Epigenetics and the Dazzling Science of NAD+ with Dr Ross Grant

Evolving Past Alzheimer's

This week's guest is Dr Ross Grant, a clinical professor of medicine at Sydney Adventist in Sydney, Australia. He is considered one of the world's foremost authorities on NAD+ science and therapeutics.

Fair warnings: this episode is deeply technical and scientific, but during the last 15 minutes of the interview Dr Grant speculates on how NAD+ might be beneficial directly to Alzhiemer's (and Parkinson's patients). ALSO, we apologize for the sound quality of this episode. we are working to bring you better quality sound with each episode.

NAD+ or Nicotinamide Adenine Dinucleotide is a molecule necessary for a huge number of biological processes supporting human life. NAD+ levels decrease as we age. The body produces NAD+, but in addition to the natural decline in production, as we age there is also likely an increased need for NAD+ that is beyond our bodies ability to produce.

Key Biologic Processes where NAD+ is involved

1. Repair of the DNA (single base pairs) via PARP (Poly-ADP ribose polymerase)
2. Energy Production Enzymes
3. Redox-Repair Enzymatic activity
4. Epigenetical Switch - controlling gene expression especially of SIRT1 activity.
5. Immune system regulation/repair - especially relevant in Alzheimers where the immune systems and inflammation appear to be overactive making self repair more difficult.
6. Activate Tankyrase in order to extend telomeres.
7. It may act as a direct neurotransmitter in the brain and nervous system.

In an aging brain, inflammation and susceptibility to oxidative stress increase. As this happens, NAD+ levels drop and the brain loses NAD+'s sponsorship of longevity genes and mitochondrial support via sirtuin activity all contributing to eventual cell death.

Taking or using an outside source of NAD+ seems less likely to help someone if they have a lot of free radical damage (super oxide activity where oxygen free radicals are doing damage) occurring.

Caloric Restriction is one of the only scientifically proven methods to reduce damage from oxidative stress. When there is excess caloric intake (i.e. eating too much) or eat poor quality food our usable NAD+ is "tied up" in a less usable form called NADH.

Intake of excess and/or poor quality calories (i.e. bad food) gives rise to excess free radicals in the body. This occurs as cell turnover and reproduce themselves over time. Each "generation" of cells in our bodies (sometimes just hours or days later) will be made with increasing damage from these free radicals being made from a poor diet, so when this generation of cells is produced they are produced as damaged goods and effectively tie up NAD+. This increasing injury over time is known as "aging" and it depletes the body of its usable NAD+.

SIRT1 - Sirtuin (Silent Information Regulators) are able to switch on and off genes, including those that produce anti-oxidant capabilities in the body. When the body gets too many calories or the wrong kind of calories these genes - through an epigenetic mechanism known as acetylation - get down shifted and aren't able to protect us like they are designed to because the NAD+ and materials that turn them on are "busy" (ie they take the form of NADH). Being busy renders them unable to "hit the activation switch" as it were.

In general, mitochondria (energy producing parts of cells) seem to function less efficiently over time (ie aging). Some of the earliest changes in Alzheimer's occur in the mitochondria. The brain has an inordinate number of mitochondria relative to the rest of the body. NAD picks up electrons through a mitochondrion in a fairly efficient way to create energy currency in the body. Over time, this process can breakdown and become "leaky." Nutrient rich, energy limited diets (healthy, modest portions) seems to be one way to minimize these inefficiencies over time (i.e caloric restriction).

Mitochondrial Biogenesis -is the process of adding mass and function to the mitochondria (energy producing parts of our cells). Mitochondria are known to "crash" and are susceptible to damage early on in Alzheimer's. You can increase available NAD by increasing the bodies production of NAD 1) from Tryptophan 2) from over the counter forms of NAD.

Practically- these 3 forms can be bought over the counter:

1) Nicotinamide Riboside

2) Nicotinamide mononucleotide

3) Niacin

Dr Grant mentioned about 350mg may be a responsible dose, but also cautioned that some oral forms of Nicotinamide may end up stacking up and having the opposite effects that are intended (eg blocking sirtuin and PARP pathways), so you will - as always - definitely want to consult with your healthcare practitioner before trying this.

Each one of these three forms can increase the NAD inside our cells. But just supplementing with NAD without addressing other lifestyle factors of a good diet, proper sleep, enough exercise and stress reduction can lead to a build up of a recycling chemical in the body called, homocysteine which is associated with Alzheimer's, heart disease and other health issues.

Currently, there are only a few research institutions in the world that can truly measure NAD. It is unfortunately not widely available outside a research setting. According to Dr Grant, Dr Charles Brenner lab at the University of Iowa is the most reliable in the United States

IV (intravenous) NAD+ is being administered through a variety of clinical outlets in the US under medical supervision. This might be the most useful way to use it in neurodegenerative diseases like Alzheimer's and Parkinson's.

To learn more about NAD+

https://medicalsciences.med.unsw.edu.au/people/dr-ross-grant

http://www.springfieldwellnesscenter.com/

http://www.nadtreatmentcenter.com/nad-research/